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Gallbladder cancer is a rare but serious disease in which malignant (cancerous) cells form in the tissues of the gallbladder. A gallbladder tumour or neoplasm refers to an abnormal growth in the gallbladder, which may be benign or malignant. The gallbladder is a small, pear-shaped organ located beneath the liver that stores and releases bile, a fluid that helps digest fats.

The chance of cure is good when gallbladder cancer is diagnosed in its early stages. However, most gallbladder cancers are found when they have progressed to a late stage, in which the prognosis is often poor. Approximately four in five patients with gallbladder cancer are diagnosed in the advanced or metastatic stage. The five-year relative survival rate of patients with the condition is around 15-20% if diagnosed in the early stage, but less than 5% if diagnosed in the advanced stage

The condition is difficult to diagnose and tends to present late as it may cause no symptoms in the early stages. In addition, due to the deep location of the gallbladder in the human body, it is easier for gallbladder cancer to grow without being detected. It can spread to nearby tissues or other parts of the body, through the lymphatic system or the blood's circulatory system.

How prevalent is gallbladder cancer?

Gallbladder cancer is uncommon, but its incidence varies by region. It is more frequently observed in Central and South America, Eastern Europe and Southeast Asia. Gallbladder cancer is the 22^nd most common cancer worldwide. It is the 23^rd most common cancer in men and the 20^th most common cancer in women. It accounts for about 1.7% of all cancer mortality and approximately 3.5 million disability-adjusted life years (the loss of the equivalent of one year of full health) globally.

In Singapore, gallbladder cancer is rare, affecting 1.7 out of every 100,000 people.

It is more commonly diagnosed in older adults and individuals with specific risk factors such as gallstones or chronic inflammation of the gallbladder. 

The signs and symptoms of gallbladder cancer are not always apparent in its early stages. When symptoms do appear, they may include:

• Abdominal pain, particularly in the upper right side, which may be persistent or intermittent.
• Unexplained weight loss
• Jaundice, or yellowing of the skin and eyes, caused by bile duct obstruction.
• Nausea and vomiting, especially if the cancer has progressed and is affecting digestion.
• Loss of appetite, which may contribute to weight loss and general weakness.
• Bloating or a sense of fullness in the abdomen, even after eating small amounts.
• Fever, which may indicate infection or inflammation associated with gallbladder cancer.
  

There is no known way to prevent most gallbladder cancers. Many of the known risk factors for gallbladder cancer (age, sex, ethnicity, bile duct defects) are beyond one's control.

The following measures may help to lower the risk of developing the condition:

• Maintain a healthy weight.
• Follow a balanced diet that includes plenty of fruits, vegetables and whole grains, and limit or avoid processed meats, sugary drinks and highly processed foods.
• Avoid excessive consumption of fried and fatty foods.
• Avoid excessive consumption of alcohol.
• Avoid unhealthy habits such as smoking.
  

Early-stage gallbladder cancer can be difficult to detect, and its diagnosis often occurs incidentally during imaging for unrelated conditions or after gallbladder removal for gallstones.

Diagnostic tests for gallbladder cancer include:

• Blood tests: Liver function tests measure bilirubin and enzymes (alkaline phosphatase, AST, ALT, and GGT) to assess bile duct obstruction and liver health. Coagulation tests (PT, PTT, INR) may also be performed. Tumour markers such as CA 19-9 and CEA can sometimes be elevated in gallbladder cancer, but they are not specific and may also rise due to other conditions. These markers can be useful for monitoring treatment response in diagnosed cases.
• Ultrasound: A non-invasive imaging technique to detect abnormalities in the gallbladder.
• CT scan / MRI: Provides detailed images to evaluate the extent and stage of disease.
• Endoscopic retrograde cholangiopancreatography (ERCP): A specialised procedure that allows for examination of bile ducts and potential biopsies.
• Biopsy: If a suspicious mass is detected, a biopsy may be performed to confirm malignancy.
  

Treatment depends on the stage of cancer and the overall health of the patient. Treatment options include:

Surgery

Early-stage gallbladder cancer may be treated with cholecystectomy (gallbladder removal), often including nearby tissues and lymph nodes.

If the cancer is advanced and inoperable, palliative surgery or procedures may be performed to relieve symptoms. Such options include:

• Biliary bypass: Reroutes bile flow around a blockage to relieve jaundice and abdominal discomfort.
• Endoscopic stent placement: A plastic or metal stent is inserted into the bile duct to keep it open, allowing bile to drain into the intestine
• Percutaneous biliary drainage: A procedure where a tube is inserted through the skin into the liver to drain bile when endoscopic stenting is not feasible, allowing bile to drain into an external bag. Subsequent stenting may be able to be performed if the drainage can be internalised.

Radiation therapy

External beam radiation therapy uses high-energy rays to target cancer cells and shrink tumours, either as a primary treatment or after surgery to reduce recurrence risk if resection margins are involved.

Chemotherapy

Systemic chemotherapy, using drugs such as Gemcitabine and Cisplatin, or 5-Fluorouracil based chemotherapy, is administered orally or intravenously to slow cancer progression and shrink tumours, particularly when surgery is not an option.

Targeted therapy

This approach uses drugs that targets specific genetic mutations in cancer cells. For example, ivosidenib targets IDH1 mutations, while infigratinib and pemigatinib target FGFR2 fusions. These are typically used in patients with advanced or inoperable disease who test positive for these mutations on next generation sequencing.

Immunotherapy

Immune checkpoint inhibitors such as pembrolizumab (PD-1) and durvalumab (PD-L1) help the immune system recognise and attack cancer cells. These may be considered for advanced-stage or recurrent gallbladder cancer that no longer responds to standard treatments, or in patients with certain mutations or deficient mismatch repair proteins.